HIV-1 RNA levels and the development of clinical disease

The prognostic value of HIV RNA levels for predicting clinical disease independently of the CD4 lymphocyte count in patients on antiretroviral therapy was assessed. For 620 patients randomized in the North American NUCA3001 and NUCA3002 trials of lamivudine, HIV RNA levels were measured (median, seven measures per patient) and CD4 counts were assessed at a central laboratory (median, 13 counts per patient). Patients were in the 1993 Centers for Disease Control and Prevention (CDC) stages A (n = 439), B (n = 135) or C (n = 46) at baseline. For patients who were in CDC stage A at baseline we considered the ability of HIV RNA levels and CD4 counts to predict the development of CDC stage B or C disease. A Cox proportional hazards model was used. In a second analysis, patients who were AIDS-free at baseline were considered, and the endpoint was AIDS (CDC stage C). Patients' initial CD4 counts ranged (5-95% centiles) from 104 to 529x10 super(6)/l (median, 274x10 super(6)/l) and HIV RNA levels from 1900 to 339 680 copies/ml (median, 44 240 copies/ml). For the first analysis, with CDC stage B or C disease as endpoint, both the most recent HIV RNA level and CD4 count predicted the development of clinical disease [relative hazard (RH) for HIV RNA, 1.96 per 10-fold difference in HIV RNA; 95% confidence interval (Cl), 1.41-2.73; P = 0.0001; and RH for CD4 count, 1.82 per twofold difference in CD4 count; 95% Cl, 1.27-2.56; P = 0.0009]. When both HIV RNA and CD4 count were included in a multiple regression model, both markers provided information additional to that given by the other (RH for HIV RNA, 1.75; 95% Cl, 1.23-2.50; P = 0.002; and RH for CD4 count, 1.40; 95% Cl, 0.95-2.07; P = 0.09). In the second analysis, with AIDS as endpoint, both HIV RNA level (P = 0.02) and CD4 count (P = 0.004) were independently associated with clinical progression. These results were essentially unchanged after adjustment for treatment arm (zidovudine/lamivudine versus control arms). The HIV RNA level shows ability to predict the development of clinical disease and may thus be of importance in addition to the CD4 count in patient monitoring.